Restoration of hypoxic pulmonary vasoconstriction following normoxia in isolated dog lungs occurs in the presence but not in the absence of prostaglandin synthesis inhibitors.

We examined the possibility that eucapnic (6% CO2) alveolar hypoxia (3% O2) in isolated dog lungs not only produces an increase in pulmonary vascular resistance but also initiates the subsequent prostaglandin (PG) dependent reduction in this hypoxic pulmonary vasoconstriction (HPV). We determined that a reduction in HPV occurred after 45 min including a 35-min period of hypoxia (prolonged hypoxia), after 45 min of intermittent hypoxia, and after 45 min of normoxia (14% O2). These reductions were PG dependent, since they were reversed or prevented by PG synthesis inhibitors in the autologous blood perfusate. In addition to the PG-dependent reduction that required 45 min to develop, a separate reduction in HPV also occurred. This reduction occurred during prolonged hypoxia, was not prevented by PG synthesis inhibitors, was reversed after 6 min of normoxia, and was reproduced in a second period of prolonged hypoxia. We conclude that alveolar hypoxia did not initiate the PG-dependent reduction in HPV, since it occurred after normoxia as well as after hypoxia. However, hypoxia appeared to contribute to a separate PG-independent reduction in HPV, since this reduction was initiated and maintained exclusively during prolonged hypoxia and was unaffected by PG synthesis inhibitors.